Despite a myriad of screening tests available, colorectal cancer (CRC) remains the second leading cause of cancer deaths among Americans. Approximately half the population does not undergo any CRC screening because of cost, access and concerns about discomfort with both the procedure and colonic purge. Flexible sigmoidoscopy (endoscopic evaluation of the distal colon) is performed in the community and has many advantages over other recommended tests (e.g. colonoscopy, CT colography) such as being relatively inexpensive, more widely available (performed by primary care physicians) and proven efficacy at decreasing both CRC mortality and incidence. However, flexible sigmoidoscopy is insensitive in women given their predilection for proximal neoplasia. Indeed, while flex sig identifies two-thirds of advanced adenomas in men, it only detects one-third in women highlighting the need for adjunctive approaches. Our multi-disciplinary CRC prevention group has focused on bridging novel optical technologies to clinical practice. Using 4-dimensional elastic light scattering fingerprinting (4D-ELF), we published that in CRC models, the peri-cryptal capillary blood content was increased prior to any histological abnormalities (a phenomena we termed EIBS (early increase in blood supply). We developed an endoscopically- compatible fiber-optic probe and demonstrated that EIBS was detectable at a distance from neoplastic lesions. In the rectum, EIBS was detectable in patients harboring advanced neoplasia elsewhere in their colon. Importantly, rectal EIBS was more robust in women (~60% increase versus neoplasia-free controls) than men (~25%) for proximal advanced neoplasia (that was not visualizable by flexible sigmoidoscope). We, therefore, hypothesize that rectal EIBS measurement will detect advanced proximal neoplasia in women. We will obtain rectal EIBS analysis on women undergoing colonoscopy. We will identify diagnostic EIBS parameters and determine the impact of demographic factors (e.g. age, race, smoking, medication use) on these markers. This data will be used to formulate a prediction rule for advanced proximal adenomas. We will then prospectively validate this prediction rule on a separate cohort of women simulating real world flexible sigmoidoscopy screening conditions prior to full colonoscopy. This will provide the rationale to performing future multi-center trials of rectal EIBS as an adjunct to flex sig in women. If successful, this practical and relatively inexpensive approach may be pivotal for the resurgence of flexible sigmoidoscopy as an accurate, cost-effective and patient-friendly CRC screening option in women. PUBLIC HEALTH RELEVANCE: Flexible sigmoidoscopy as a colorectal cancer screening test is widely available but inaccurate at detecting premalignant polyps in women, largely because women's polyps tend to be located out of reach of the flexible sigmoidoscope. We believe that assessing the superficial blood supply in the visually normal rectum may be uniquely able to sense these lesions further up in the colon of women. If successful, this relatively inexpensive, easy-to-use test may be an adjunct to flexible sigmoidoscopy thereby allowing accurate and cost-effective colorectal cancer screening for women.